The SPORE in Breast Cancer at Duke University is entering its third and final year. We are answering an RFA to renew the Duke SPORE for two additional years, bringing our Program into cycle with other NCI SPORE sites. Our renewal includes six major Projects, four Core Resources, a Pilot Project and a Career Development Award. The emphasis of our SPORE is in two major areas of research: the genetics of breast cancer susceptibility and the development of new therapeutics. Three Projects related to susceptibility genetics. Project 2 investigate the function the function of BRCA1 and its potential role in sporadic breast cancer. Expression of BRCA1 will be assessed in clinical cancer, modulated in experimental cell lines and examined during progression of the cell cycle. Project 3 will conclude a randomized trial of counseling which compares standard informed consent materials to education information tailored and the individual patient. Baseline descriptive data and the results of the randomized trial will be analyzed in years four and five. Project 4 competes for inclusion in the SPORE; this project was disallowed after the first year. The Project developed a statistical algorithm to calculate the carrier probability for breast and ovarian susceptibility based upon characteristics of the family history. This algorithm will be improve, validated and translated into clinical utility during our last two years. Core 1 has developed a family ascertainment procedure, including an epidemiological questionnaire and data management system. A genetic testing laboratory can determine sequence alterations in BRCA1/2 rapidly and at low cost, providing free testing to Project 3 subprojects. Three Projects are concerned with new therapies for breast cancer. Project 1 has discovered a new estrogen antagonist with improve therapeutic characteristics compared to tamoxifen. A clinical trial is planned. Laboratory work concerns the pre-clinical efficacy and mechanism of action of this new drug. Project 5 continues to characterize anti-tumor cellular reactivities in breast cancer patients and proposes a vaccination trial in cancer patients. Project 6 has chosen to focus on inhibitors of endothelial growth factor receptors, working toward small molecule inhibitors that have clinical utility. Biomarkers of angiogenesis will be developed and clinically tested. Core 2 for Information Management has developed the Family Cancer Database, the Tissue Resources Database and provides statistical support for major Projects, in particular the large amount of data generated in Project 3. Core 4 provides frozen and paraffin embedded material from more than 100 patients and operates a modern preclinical animal testing facility used by Projects 1 and 6 for large scale therapeutic trials. A Pilot Project Program and Cancer Development Award are described. Core 3 administers the SPORE and includes a strong emphasis on education, continuous improve on research and involvement of Patient Advocates.